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Blood-brain barrier...
Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients : effect of polymorphisms in the ABCB1 gene
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van Assema, Daniëlle ME (författare)
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- Lubberink, Mark (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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Rizzu, Patrizia (författare)
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visa fler...
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van Swieten, John C (författare)
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Schuit, Robert C (författare)
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- Eriksson, Jonas (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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Scheltens, Philip (författare)
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Koepp, Matthias (författare)
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Lammertsma, Adriaan A (författare)
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van Berckel, Bart NM (författare)
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: EJNMMI Research. - 2191-219X. ; 2
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- BACKGROUND: P-glycoprotein is a blood-brain barrier efflux transporter involved in the clearance of amyloid-beta from the brain and, as such, might be involved in the pathogenesis of Alzheimer's disease. P-glycoprotein is encoded by the highly polymorphic ABCB1 gene. Single-nucleotide polymorphisms in the ABCB1 gene have been associated with altered P-glycoprotein expression and function. P-glycoprotein function at the blood-brain barrier can be quantified in vivo using the P-glycoprotein substrate tracer (R)-[11C]verapamil and positron emission tomography (PET). The purpose of this study was to assess the effects of C1236T, G2677T/A and C3435T single-nucleotide polymorphisms in ABCB1 on blood-brain barrier P-glycoprotein function in healthy subjects and patients with Alzheimer's disease.METHODS: Thirty-two healthy subjects and seventeen patients with Alzheimer's disease underwent 60-min dynamic (R)-[11C]verapamil PET scans. The binding potential of (R)-[11C]verapamil was assessed using a previously validated constrained two-tissue plasma input compartment model and used as outcome measure. DNA was isolated from frozen blood samples and C1236T, G2677T/A and C3435T single-nucleotide polymorphisms were amplified by polymerase chain reaction.RESULTS: In healthy controls, binding potential did not differ between subjects without and with one or more T present in C1236T, G2677T and C3435T. In contrast, patients with Alzheimer's disease with one or more T in C1236T, G2677T and C3435T had significantly higher binding potential values than patients without a T. In addition, there was a relationship between binding potential and T dose in C1236T and G2677T.CONCLUSIONS: In Alzheimer's disease patients, C1236T, G2677T/A and C3435T single-nucleotide polymorphisms may be related to changes in P-glycoprotein function at the blood-brain barrier. As such, genetic variations in ABCB1 might contribute to the progression of amyloid-beta deposition in the brain.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
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van Assema, Dani ...
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Lubberink, Mark
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Rizzu, Patrizia
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van Swieten, Joh ...
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Schuit, Robert C
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Eriksson, Jonas
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visa fler...
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Scheltens, Phili ...
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Koepp, Matthias
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Lammertsma, Adri ...
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van Berckel, Bar ...
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visa färre...
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